Megaloblastic anaemia

Question 1

What is macrocytosis

Answer 1

An increase in the size of RBC . The size of RBC can be reflected by MCV and morphology reviewed on peripheral blood smear

Question 2

What is megaloblastic anemia and what is the cause

Answer 2

• A group of disorders characterized by certain morphological changes in the developing RBC (asynchronous maturation ).
• Caused by a defect in DNA synthesis which affects all rapidly developing cells. Most commonly caused by Vit B12 def

Question 3

There are 2 types of causes of macrocytic anemia ( result from abnormal erythropoiesis ) and other causes: Megaloblastic erythropoiesis & macronormoblastic erythropoiesis

Answer 3

1. Causes megaloblastic erythropoiesis :
   * Vit B12 def
   * Folate def
   * abnormal Vit B12 / folate metabolism
   * antifolate drugs
   * Defects of DNA synthesis inherited and acquired (zidovudine )
2. Macronormoblastic erythropoiesis :
   * alcohol
   * liver disease
   * Myelodysplastic syndrome
   * Myxoedema
   * aplastic anemia
   * multiple myeloma
3. Other causes
   * pregnancy
   * neonates
   * reticulocytes
   * smoking

Question 4

Discuss the biochemical basis of megaloblastic

Answer 4

*Deficiency of folate / Vit B12 is not converted into deoxythymidine monophosphate (dTMP ) resulting in a decreased supply of deoxythymidine triphosphate for DNA synthesis

Question 5

Discuss folate absorption

Answer 5

*Absorbed in the upper small intestine ( in the duodenum and jejunum ) through the folate transporter proteins.
*Folate is easily destroyed by heat and the body stores last 4 months and can rapidly finish
*

Folate is converted into 5 methyl THF within the small intestine before they enter the plasma
*1/3 of folate is transported bound to the albumin and 2/3 is unbound

*daily requirement: 100 ug

Question 6

Folate polyglutamate acts as co-enzyme involved in :

Answer 6

• Purine synthesis
• Pyrimidine synthesis
• Amino acid conversion to homocysteine to methionine

Question 7

Causes of folate def

Answer 7

• Dietary ,alcoholism ,poverty , infants fed on goat milk
• malabsorption
• antifolate drugs (drugs wgich inhibit dihydrofolate reductase )
• pregnancy ,lactation ,prematurity
• haematological diseases ,malignancy ,inflammation and metabolic disease
• Excess urinary loss ,acute liver disease ,dialisus

Question 8

Sources of Vit B12 (cobalamin )

Answer 8

*synthesized solely by a microorganism, liver, meat, fish, chicken, and dairy products.

• stores are enough for 3-4 years
• daily requirement: 1-5 ug

Question 9

Which proteins bind to cobalamin

Answer 9

• Intrinsic factors: Gastric parietal cells :
• Transcobalamin: Synthesized by the liver, macrophages, and ilium
• Haptocorrins :
• R binder and TCI : transport in plasma to lievre

Question 10

Cobalamin absorption

Answer 10

*Cobalamin enters the portal blood bound to 1 of two transporting proteins
: transcobalamin and haptocorrins
*Cobalamin - transcobalamin complex binds to a membrane receptor present on the surface of many cells
*transcobalamin is digested and cobalamin is released

Question 11

Causes of severe cobalamin deficiency

Answer 11

• Vagens
• Malabsorption
• pernicious anaemia
• gastrectomy ( full/half)
• Congenital deficiency or functional abnormality
• ileal resection and Chron s disease
• fish tape
• Transcobalamin deficiency

Question 12

Clinical findings common to all megaloblastic anemias

Answer 12

1. Asymptomatic
2. Anaemia: weakness, fatigue, palpitations, light-headed and shortness of breath
3. Thrombocytopenia: may cause bruising
4. Leucopenia: May predispose to infection
5. Jaundice due to increased unconjugated hyperbilirubinaemia
6. Angular stomatitis, anorexia

Question 13

T/F: Cobalamin and folate def affects all dying cells

Answer 13

T, especially bone marrow followed by epithelial surfaces of the mouth, stomach, and genital tract.

The cells are large and many are dying

Question 14

How to prevent neural tube defects in fetus

Answer 14

Supplementation with folic acid from conception for the first 12 weeks

Question 15

Laboratory diagnosis of folate and cobalamin def

Answer 15

• RBC : D
• Hg : D
• HCT : D
• MCV : I
• MCHC : Normal
• RDW : I
• WBC : D
• PLt count : D

Pancytopenia: anaemia, neutropenia and thrombocytopenia

Question 16

Biochemical evidence of ineffective erythropoiesis includes :

Answer 16

*Unconjugated hyperbilirubinemia
*decreased haptoglobin levels
*Increased urine urobilinogen
*Raised LDH
These finds are noted in certain hemolytic anemia

In megaloblastic, there is ineffective granulopoiesis and megakaryopoiesis resulting in pancytopenia

Question 17

Diagnosing folate deficiency

Answer 17

*Serum levels :
> low
> affected by diet
>inadequate intake for one week can result in low levels

• RED CELL Folate :
• reflect body stores

*Megaloblastic anaemia resulting from folate def RBC folate is low and folate serum levels low

Question 18

Diagnosis of cobalamin deficiency

Answer 18

*low levels with megaloblastic anemia, serum levels may be high and RBC folate levels low
*serum methylmalonic acid and homocysteine levels are increased
*

Question 19

Treament for folate and cobalamin

Answer 19

*replacement therapy

> For patients with severe symptoms :

• Blood for both folate and cobalamin should be taken
• Bone marrow aspirate and trephine biopsy
• Replacement therapy: High doses of folate in presence of cobalamin def may aggregate neuropathy

> Avoid blood transfusion if possible :

• packed cells should be given slowly. Patients must be closely monitored for pulmonary edema and circulatory overload
• Platelets for patients with thrombocytopenia

Question 20

Treatment for cobalamin deficiency

Answer 20

• Body stores should be replaced after 1000ug intramuscular injections of hydroxycobalamin given every 3-7 days
• 1000ug imi every 3 months

Question 21

Treatment for folate deficiency

Answer 21

• given orally
• dose : 5-15 mg daily but exclude cobalamin def .

check cobalamin levels annually

5 mg daily for pregnant women